What lab values and tests differentiate iron deficiency anemia (IDA) from other types of anemia?

Differentiating Iron Deficiency Anemia from Other Types of Anemia Using Laboratory Values

Iron deficiency anemia (IDA) can be differentiated from other types of anemia through a combination of complete blood count parameters and specific iron status tests, with serum ferritin being the most powerful diagnostic test for iron deficiency.

Key Laboratory Tests for Iron Deficiency Anemia

Complete Blood Count (CBC) Parameters

• Hemoglobin (Hb) concentration and hematocrit (Hct) are decreased in anemia but are late indicators of iron deficiency 1
• Mean Corpuscular Volume (MCV): Low in IDA (microcytosis) 1
• Red Cell Distribution Width (RDW): Elevated in IDA 1, 2
• Red Blood Cell (RBC) count: May be decreased in severe IDA 2
• Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC): Decreased in IDA 2, 3

Iron Status Tests

• Serum ferritin: The most powerful diagnostic test for iron deficiency 1
  • <30 μg/L indicates iron deficiency in the absence of inflammation 1
  • <100 μg/L may still indicate iron deficiency in the presence of inflammation 1
• Transferrin saturation: <16% suggests iron deficiency 1
• Serum iron: Decreased in IDA 1, 4
• Total Iron Binding Capacity (TIBC): Increased in IDA 1
• Serum transferrin receptor (sTfR): Elevated in iron deficiency, normal or low in anemia of chronic disease 1, 4
• Reticulocyte hemoglobin content (CHr): Early marker of iron-deficient erythropoiesis 5

Differentiating IDA from Other Common Anemias

Anemia of Chronic Disease (ACD)

• Serum ferritin: >100 μg/L in ACD 1
• Transferrin saturation: <16% in ACD (similar to IDA) 1
• Serum transferrin receptor: Normal or low in ACD (elevated in IDA) 1
• Inflammatory markers: Elevated CRP, ESR, or leukocytosis in ACD 1
• Combined IDA and ACD: Ferritin between 30-100 μg/L with low transferrin saturation 1

Thalassemia

• MCV: Markedly low, often out of proportion to the degree of anemia 1
• RBC count: Normal or elevated (unlike IDA where it's normal or decreased) 1
• Hemoglobin electrophoresis: Abnormal pattern specific to the type of thalassemia 1
• Serum ferritin: Normal or elevated (unlike IDA) 1

Vitamin B12 or Folate Deficiency Anemia

• MCV: Elevated (macrocytosis) 1
• Serum B12 or folate levels: Decreased 1
• Reticulocyte count: Low or normal 1
• Serum ferritin: Normal (unless concurrent iron deficiency) 1

Hemolytic Anemia

• Reticulocyte count: Elevated 1
• Lactate dehydrogenase (LDH): Elevated 1
• Haptoglobin: Decreased 1
• Bilirubin: Elevated (indirect) 1

Diagnostic Algorithm for Anemia Workup

1. Initial screening: Complete blood count with Hb, Hct, MCV, and RDW 1

2. If anemia is detected (Hb <12 g/dL in women, <13 g/dL in men) 1, 6:

   • Classify based on MCV:
     • Microcytic (low MCV): Suspect IDA, thalassemia, or ACD 1
     • Normocytic (normal MCV): Consider early IDA, ACD, or mixed deficiency 1, 3
     • Macrocytic (high MCV): Consider B12/folate deficiency 1

3. For suspected IDA (microcytic or normocytic anemia):

   • Measure serum ferritin, transferrin saturation, and CRP 1
   • Interpret results:
     • Ferritin <30 μg/L without inflammation: Confirms IDA 1
     • Ferritin 30-100 μg/L with inflammation (elevated CRP): Possible combined IDA and ACD 1
     • Ferritin >100 μg/L with low transferrin saturation: Likely ACD 1

4. If diagnosis remains unclear:

   • Consider measuring serum transferrin receptor (sTfR) 1, 4
   • Consider reticulocyte hemoglobin content (CHr) if available 5
   • Therapeutic trial of iron supplementation: A 1-2 g/dL increase in Hb after 1 month confirms IDA 1, 6
   • In rare cases, bone marrow examination may be necessary 1, 4

Common Pitfalls and Caveats

• Relying solely on Hb and Hct can miss early iron deficiency, as these are late indicators 1, 3
• Inflammation can elevate ferritin levels, masking iron deficiency 1
• Race-specific differences exist in Hb distribution; black patients may have lower Hb levels without iron deficiency 1
• Capillary blood sampling technique can affect Hb and Hct readings; excessive squeezing of the finger can lead to falsely low values 1
• Combined deficiencies (iron + B12/folate) can result in normocytic anemia despite significant iron deficiency 1
• Chronic diseases, malignancy, and liver disease can all elevate ferritin levels despite iron deficiency 1
• Thalassemia trait is often misdiagnosed as IDA, particularly in certain ethnic groups 1